DESCRIPTION: One reason for the failure of subunit vaccine preparations is that they do not present native envelope epitopes efficiently. Immunogens such as HIV gp160 actually represent nonnative forms of the viral envelope (viral debris). It is possible that the abundance of the gp160 precursor protein even interferes with the maturation of the response to native envelope, which itself is a poor immunogen. If a novel strategy can be developed to obtain envelope immunogens targeted to stimulate a strong antibody response against native envelope and a decreased response to viral debris, protection against HIV-1 in hu-PBL-SCID mice would be achievable. There are 4 specific aims: 1) To define the quality of envelope-based immunogen using a set of monoclonal antibodies that distinguish between the native virion-associated gp120 and the nonnative viral debris gp160. 2) To improve processing of gp160 precursor in vitro and 3) to partition a large amount of envelope in its native configuration on the surface of cells or pseudovirions. 4) To transfer neutralizing antisera in hu-PBL-SCID mice in order to assess protection against HIV-1 in vivo.